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UniProtKB/Swiss-Prot P61769: Variant p.Asp96Asn

Beta-2-microglobulin
Gene: B2M
Chromosomal location: 15q21-q22.2
Variant information

Variant position:  96
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Aspartate (D) to Asparagine (N) at position 96 (D96N, p.Asp96Asn).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and acidic (D) to medium size and polar (N)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  Amyloidosis 8 (AMYL8) [MIM:105200]: A form of hereditary generalized amyloidosis. Clinical features include extensive visceral amyloid deposits, renal amyloidosis resulting in nephrotic syndrome, arterial hypertension, hepatosplenomegaly, cholestasis, petechial skin rash. There is no involvement of the nervous system. {ECO:0000269|PubMed:22693999}. Note=The disease is caused by mutations affecting the gene represented in this entry. Apart from the presence of causative mutations, beta-2-microglobulin may adopt the fibrillar configuration of amyloid when its serum levels are persistently high. High beta(2)-microglobulin serum levels result in amyloidosis in patients on long-term hemodialysis (PubMed:7918443). In contrast to patients with dialysis-related amyloidosis, patients with hereditary amyloidosis have normal circulating concentrations of beta2-microglobulin (PubMed:22693999). {ECO:0000269|PubMed:22693999, ECO:0000269|PubMed:7918443}.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In AMYL8; reduced stability; in contrast to the wild-type, the mutant aggregates into fibrils with classic amyloid-like properties under physiologic solvent conditions.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  96
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  119
The length of the canonical sequence.

Location on the sequence:   FSKDWSFYLLYYTEFTPTEK  D EYACRVNHVTLSQPKIVKWD
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         FSKDWSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWD

Gorilla                       FSKDWSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWD

Rhesus macaque                FSKDWSFYLLYYTEFTPNEKDEYACRVNHVTLSGPRTVKWD

Chimpanzee                    FSKDWSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWD

Mouse                         FSKDWSFYILAHTEFTPTETDTYACRVKHASMAEPKTVYWD

Rat                           FSKDWSFYILAHTEFTPTETDVYACRVKHVTLKEPKTVTWD

Pig                           FSKDWSFYLLVHTEFTPNAVDQYSCRVKHVTLDKPKIVKWD

Bovine                        FSKDWSFYLLSHAEFTPNSKDQYSCRVKHVTLEQPRIVKWD

Rabbit                        FNKDWSFYLLVHTEFTPNNKNEYSCRVKHVTLKEPMTVKWD

Sheep                         FSKDWSFYLLSHAEFTPNSKDQYSCRVNHVTLTQPKIVKWD

Cat                           FNRDWTFYLLVHTEFTPTVEDEYSCQVNHTTLSEPKVVKWD

Horse                         FSKDWSFYLLVHTDFTPNGVDEYSCRVQHSTLKDPLIVKWD

Chicken                       FNDDWTFQRLVHADFTPSSGSTYACKVEHETLKEPQVYKWD

Xenopus laevis                FQHNWKYYTTKSTHVHIDKGDKVECVVSHNG-NPSKKYRLD

Zebrafish                     FEKGWQFHLTKSVAFTPEKGDEYTCSVRH--MKETKKFSWE

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 21 – 119 Beta-2-microglobulin
Chain 22 – 119 Beta-2-microglobulin form pI 5.3
Domain 25 – 113 Ig-like C1-type
Glycosylation 78 – 78 N-linked (Glc) (glycation) lysine; in vitro
Glycosylation 111 – 111 N-linked (Glc) (glycation) lysine; in vitro
Glycosylation 114 – 114 N-linked (Glc) (glycation) lysine; in vitro
Disulfide bond 45 – 100
Mutagenesis 79 – 79 D -> P. Increases tendency towards amyloid formation.
Mutagenesis 80 – 80 W -> G. Decreases tendency towards amyloid formation.
Mutagenesis 80 – 80 W -> V. Increases tendency towards amyloid formation.


Literature citations

Hereditary systemic amyloidosis due to Asp76Asn variant beta2-microglobulin.
Valleix S.; Gillmore J.D.; Bridoux F.; Mangione P.P.; Dogan A.; Nedelec B.; Boimard M.; Touchard G.; Goujon J.M.; Lacombe C.; Lozeron P.; Adams D.; Lacroix C.; Maisonobe T.; Plante-Bordeneuve V.; Vrana J.A.; Theis J.D.; Giorgetti S.; Porcari R.; Ricagno S.; Bolognesi M.; Stoppini M.; Delpech M.; Pepys M.B.; Hawkins P.N.; Bellotti V.;
N. Engl. J. Med. 366:2276-2283(2012)
Cited for: INVOLVEMENT IN AMYL8; VARIANT AMYL8 ASN-96; CHARACTERIZATION OF VARIANT AMYL8 ASN-96;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.